Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex

被引:376
作者
Parker, JS [1 ]
Roe, SM [1 ]
Barford, D [1 ]
机构
[1] Inst Canc Res, Chester Beatty Labs, Sect Struct Biol, London SW3 6JB, England
基金
英国惠康基金;
关键词
D O I
10.1038/nature03462
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
RNA interference and related RNA silencing phenomena use short antisense guide RNA molecules to repress the expression of target genes(1,2). Argonaute proteins(3), containing amino-terminal PAZ (for PIWI/Argonaute/Zwille) domains and carboxy-terminal PIWI domains, are core components of these mechanisms. Here we show the crystal structure of a Piwi protein from Archaeoglobus fulgidus (AfPiwi) in complex with a small interfering RNA (siRNA)-like duplex, which mimics the 5 ' end of a guide RNA strand bound to an overhanging target messenger RNA. The structure contains a highly conserved metal-binding site that anchors the 5 ' nucleotide of the guide RNA. The first base pair of the duplex is unwound, separating the 5 ' nucleotide of the guide from the complementary nucleotide on the target strand, which exits with the 3 ' overhang through a short channel. The remaining base-paired nucleotides assume an A-form helix, accommodated within a channel in the PIWI domain, which can be extended to place the scissile phosphate of the target strand adjacent to the putative slicer catalytic site. This study provides insights into mechanisms of target mRNA recognition and cleavage by an Argonaute-siRNA guide complex.
引用
收藏
页码:663 / 666
页数:4
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